Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression

Maria C. Demaria, Louisa Yeung, Rens Peeters, Janet L. Wee, Masa Mihaljcic, Eleanor L. Jones, Zeyad Nasa, Frank Alderuccio, Pamela Hall, Brodie C. Smith, Katrina J. Binger, Gunther Hammerling, Hang Fai Kwok, Andrew Newman, Ann Ager, Annemiek van Spriel, Michael J. Hickey, Mark D. Wright

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3 Citations (Scopus)

Abstract

Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53−/− mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53−/− B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53−/− B cells and reduced stability of L-selectin on Cd53−/− T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53−/− mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.

Original languageEnglish
Article number101104
Number of pages21
JournaliScience
Volume23
Issue number5
DOIs
Publication statusPublished - 22 May 2020

Keywords

  • Immune Response
  • Immunology
  • Molecular Mechanism of Behavior
  • Specialized Functions of Cells

Cite this

Demaria, M. C., Yeung, L., Peeters, R., Wee, J. L., Mihaljcic, M., Jones, E. L., Nasa, Z., Alderuccio, F., Hall, P., Smith, B. C., Binger, K. J., Hammerling, G., Kwok, H. F., Newman, A., Ager, A., van Spriel, A., Hickey, M. J., & Wright, M. D. (2020). Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression. iScience, 23(5), [101104]. https://doi.org/10.1016/j.isci.2020.101104